ACADM

Last updated
ACADM
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ACADM , acyl-CoA dehydrogenase, C-4 to C-12 straight chain, ACAD1, MCAD, MCADH, acyl-CoA dehydrogenase medium chain
External IDs OMIM: 607008 MGI: 87867 HomoloGene: 3 GeneCards: ACADM
Orthologs
SpeciesHumanMouse
Entrez

34

11364

Ensembl

ENSG00000117054

ENSMUSG00000062908

UniProt

P11310

P45952

RefSeq (mRNA)

NM_000016
NM_001127328
NM_001286042
NM_001286043
NM_001286044

Contents

NM_007382

RefSeq (protein)

NP_000007
NP_001120800
NP_001272971
NP_001272972
NP_001272973

NP_031408

Location (UCSC) Chr 1: 75.72 – 75.79 Mb Chr 3: 153.63 – 153.65 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a gene that provides instructions for making an enzyme called acyl-coenzyme A dehydrogenase that is important for breaking down (degrading) a certain group of fats called medium-chain fatty acids.

These fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissue. Medium-chain fatty acids are also produced when larger fatty acids are degraded.

The acyl-coenzyme A dehydrogenase for medium-chain fatty acids (ACADM) enzyme is essential for converting these particular fatty acids to energy, especially during periods without food (fasting). The ACADM enzyme functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondria of several types of tissues, particularly the liver.

The ACADM gene is located on the short (p) arm of chromosome 1 at position 31, from base pair 75,902,302 to base pair 75,941,203.

Structure

The protein encoded by the ACADM gene is ~47 kDa in size, and composed of 421 amino acids. [5]

Function

The LCAD enzyme catalyzes most of fatty acid beta-oxidation by forming a C2-C3 trans-double bond in the fatty acid. MCAD works on long-chain fatty acids, typically between C4 and C12-acylCoA. [6] Fatty acid oxidation has proven to spare glucose in fasting conditions, and is also required for amino acid metabolism, which is essential for the maintenance of adequate glucose production. [7] Furthermore, MCAD participates in fatty acid metabolism and PPAR signaling pathway. [8]

Clinical significance

Medium-chain acyl-coenzyme A dehydrogenase deficiency can be caused by mutations in the ACADM gene. More than 54 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified. [9] Many of these mutations switch an amino acid building block in the ACADM enzyme. The most common amino acid substitution replaces lysine with glutamic acid at position 329 in the enzyme's chain of amino acids (also written as Lys329Glu or K329E). [10] This mutation and other amino acid substitutions alter the enzyme's structure, reducing or abolishing its activity. Other mutations delete or duplicate part of the ACADM gene, which leads to an unstable enzyme that cannot function.

With a shortage (deficiency) of functional ACADM enzyme, medium-chain fatty acids cannot be degraded and processed. As a result, these fats are not converted into energy, which can lead to characteristic symptoms of this disorder, such as lack of energy (lethargy) and low blood sugar. Levels of medium-chain fatty acids or partially degraded fatty acids may build up in tissues and can damage the liver and brain, causing more serious complications. [11]

Related Research Articles

Medium-chain acyl-coenzyme A dehydrogenase deficiency Medical condition

Medium-chain acyl-CoA dehydrogenase deficiency is a disorder of fatty acid oxidation that impairs the body's ability to break down medium-chain fatty acids into acetyl-CoA. The disorder is characterized by hypoglycemia and sudden death without timely intervention, most often brought on by periods of fasting or vomiting.

MCAD may refer to:

Inborn error of lipid metabolism Medical condition

Numerous genetic disorders are caused by errors in fatty acid metabolism. These disorders may be described as fatty oxidation disorders or as a lipid storage disorders, and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types.

ACADVL Protein-coding gene in the species Homo sapiens

Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (VLCAD) is an enzyme that in humans is encoded by the ACADVL gene.

Acyl-CoA dehydrogenases (ACADs) are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid β-oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrate. Flavin adenine dinucleotide (FAD) is a required co-factor in addition to the presence of an active site glutamate in order for the enzyme to function.

ACADS Protein-coding gene in the species Homo sapiens

Acyl-CoA dehydrogenase, C-2 to C-3 short chain is an enzyme that in humans is encoded by the ACADS gene. This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. The ACADS gene associated with short-chain acyl-coenzyme A dehydrogenase deficiency.

ACADL Protein-coding gene in the species Homo sapiens

Acyl-CoA dehydrogenase, long chain is a protein that in humans is encoded by the ACADL gene.

Acyl-CoA

Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way, fats are converted to ATP, the universal biochemical energy carrier.

HADHA

Trifunctional enzyme subunit alpha, mitochondrial also known as hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit is a protein that in humans is encoded by the HADHA gene. Mutations in HADHA have been associated with trifunctional protein deficiency or long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.

HADHB Protein-coding gene in the species Homo sapiens

Trifunctional enzyme subunit beta, mitochondrial (TP-beta) also known as 3-ketoacyl-CoA thiolase, acetyl-CoA acyltransferase, or beta-ketothiolase is an enzyme that in humans is encoded by the HADHB gene.

Methylmalonyl CoA epimerase

Methylmalonyl CoA epimerase is an enzyme involved in fatty acid catabolism that is encoded in human by the "MCEE" gene located on chromosome 2. It is routinely and incorrectly labeled as "methylmalonyl-CoA racemase". It is not a racemase because the CoA moiety has 5 other stereocenters.

ACADSB Protein-coding gene in the species Homo sapiens

ACADSB is a human gene that encodes short/branched chain specific acyl-CoA dehydrogenase (SBCAD), an enzyme in the acyl CoA dehydrogenase family.

ETFA

The human ETFA gene encodes the Electron-transfer-flavoprotein, alpha subunit, also known as ETF-α. Together with Electron-transfer-flavoprotein, beta subunit, encoded by the 'ETFB' gene, it forms the heterodimeric electron transfer flavoprotein (ETF). The native ETF protein contains one molecule of FAD and one molecule of AMP, respectively.

ETFB Protein-coding gene in the species Homo sapiens

The human ETFB gene encodes the Electron-transfer-flavoprotein, beta subunit, also known as ETF-β. Together with Electron-transfer-flavoprotein, alpha subunit, encoded by the 'ETFA' gene, it forms the heterodimeric Electron transfer flavoprotein (ETF). The native ETF protein contains one molecule of FAD and one molecule of AMP, respectively.

ACAD8 Protein-coding gene in the species Homo sapiens

Isobutyryl-CoA dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ACAD8 gene on chromosome 11.

ACAD9 Protein-coding gene in the species Homo sapiens

Acyl-CoA dehydrogenase family member 9, mitochondrial is an enzyme that in humans is encoded by the ACAD9 gene. Mitochondrial Complex I Deficiency with varying clinical manifestations has been associated with mutations in ACAD9.

Fatty-acid metabolism disorder Medical condition

A broad classification for genetic disorders that result from an inability of the body to produce or utilize one enzyme that is required to oxidize fatty acids. The enzyme can be missing or improperly constructed, resulting in it not working. This leaves the body unable to produce energy within the liver and muscles from fatty acid sources.

Hydroxyacyl-Coenzyme A dehydrogenase

Hydroxyacyl-Coenzyme A dehydrogenase (HADH) is an enzyme which in humans is encoded by the HADH gene.

Medium-chain acyl-CoA dehydrogenase

Medium-chain acyl-CoA dehydrogenase is an enzyme with systematic name medium-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase. This enzyme catalyses the following chemical reaction

ACOT13 Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene. This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000117054 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000062908 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "ACADM – Medium-chain specific acyl-CoA dehydrogenase, mitochondrial precursor – Homo sapiens (Human) – ACADM gene & protein". www.uniprot.org.
  6. ↑ Matsubara Y, Kraus JP, Yang-Feng TL, Francke U, Rosenberg LE, Tanaka K (Sep 1986). "Molecular cloning of cDNAs encoding rat and human medium-chain acyl-CoA dehydrogenase and assignment of the gene to human chromosome 1". Proceedings of the National Academy of Sciences of the United States of America. 83 (17): 6543–7. Bibcode:1986PNAS...83.6543M. doi: 10.1073/pnas.83.17.6543 . PMC   386540 . PMID   3462713.
  7. ↑ Goetzman ES, Alcorn JF, Bharathi SS, Uppala R, McHugh KJ, Kosmider B, Chen R, Zuo YY, Beck ME, McKinney RW, Skilling H, Suhrie KR, Karunanidhi A, Yeasted R, Otsubo C, Ellis B, Tyurina YY, Kagan VE, Mallampalli RK, Vockley J (Apr 2014). "Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction". The Journal of Biological Chemistry. 289 (15): 10668–79. doi: 10.1074/jbc.M113.540260 . PMC   4036448 . PMID   24591516.
  8. ↑ Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee, MJ (May 2021). "Downregulation of fatty acid oxidation by involvement of HIF-1α and PPARγ in human gastric adenocarcinoma and its related clinical significance". Journal of Physiology and Biochemistry. 77 (2): 249–260. doi:10.1007/s13105-021-00791-3. PMID   33730333. S2CID   232300877.
  9. ↑ Pagon RA, Bird TD, Dolan CR, et al. (1993). "Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency". PMID   20301597.{{cite journal}}: Cite journal requires |journal= (help)
  10. ↑ Gregersen N, Andresen BS, Bross P, Winter V, Rüdiger N, Engst S, Christensen E, Kelly D, Strauss AW, Kølvraa S (Apr 1991). "Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli" (PDF). Human Genetics. 86 (6): 545–51. doi:10.1007/bf00201539. PMID   1902818. S2CID   9687627.
  11. ↑ Sturm M, Herebian D, Mueller M, Laryea MD, Spiekerkoetter U (2012). "Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants". PLOS ONE. 7 (9): e45110. Bibcode:2012PLoSO...745110S. doi: 10.1371/journal.pone.0045110 . PMC   3444485 . PMID   23028790.

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